A cardiac stress test is performed to measure the response of the heart to exercise or drug-induced stress. A cardiac stress test is generally performed after a patient has experienced symptoms or when cardiac ischemia or other heart disease is suspected. However patients may develop a change in the cardiac substrate over time that may not manifest in recognizable symptoms for some time. A reduced tolerance to cardiac stress may go unrecognized until a patient experiences adverse symptoms or ischemic episodes, which could result in myocardial infarction, life-threatening arrhythmias or other serious consequences. Accordingly, there remains a need for a medical device system that enables early detection of reduced tolerance to cardiac stress that may be associated with pathological changes in the cardiac substrate, allowing early clinical intervention and improved patient care.